P19784 (CSK22_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Casein kinase II subunit alpha'
Short name=CK II alpha'
EC=2.7.11.1

Gene names

Name:	CSNK2A2
Synonyms:	CK2A2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	350 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine. Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection. May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response. During mitosis, functions as a component of the p53/TP53-dependent spindle assembly checkpoint (SAC) that maintains cyclin-B-CDK1 activity and G2 arrest in response to spindle damage. Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation. Can also negatively regulate apoptosis. Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3. Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8. Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV. Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, SRF, MAX, JUN, FOS, MYC and MYB. Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function. Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1. Acts as an ectokinase that phosphorylates several extracellular proteins. During viral infection, phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV. Ref.3 Ref.4 Ref.6
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Constitutively active protein kinase whose activity is not directly affected by phosphorylation. Seems to be regulated by level of expression and localization By similarity.
Subunit structure	Heterotetramer composed of two catalytic subunits (alpha chain and/or alpha' chain) and two regulatory subunits (beta chains). The tetramer can exist as a combination of 2 alpha/2 beta, 2 alpha'/2 beta or 1 alpha/1 alpha'/2 beta subunits. Also part of a CK2-SPT16-SSRP1 complex composed of SSRP1, SUPT16H, CSNK2A1, CSNK2A2 and CSNK2B, which forms following UV irradiation. Interacts with RNPS1. Ref.3 Ref.5
Miscellaneous	Can use both ATP and GTP as phosphoryl donors. Phosphorylation by casein kinase 2 has been estimated to represent up to one quarter of the eukaryotic phosphoproteome.
Sequence similarities	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CK2 subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Apoptosis Cell cycle Transcription Transcription regulation Wnt signaling pathway
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW axon guidance Traceable author statement. Source: Reactome mitotic spindle checkpoint Inferred from mutant phenotype Ref.4. Source: UniProtKB regulation of cell cycle Inferred from electronic annotation. Source: Compara regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from direct assay PubMed 21282530. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CSNK2A1	P68400	3	EBI-347451,EBI-347804
CSNK2B	P67870	6	EBI-347451,EBI-348169
KIF5C	O60282	4	EBI-347451,EBI-717170

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 350

350

Casein kinase II subunit alpha'

PRO_0000085891

Regions

Domain

40 – 325

286

Protein kinase

Nucleotide binding

46 – 54

9

ATP By similarity

Sites

Active site

157

1

Proton acceptor By similarity

Binding site

69

1

ATP By similarity

Amino acid modifications

Modified residue

13

1

Phosphotyrosine Ref.14

Modified residue

18

1

Phosphoserine Ref.8 Ref.14

Modified residue

21

1

Phosphoserine Ref.8 Ref.14

Modified residue

97

1

N6-acetyllysine Ref.15

Modified residue

288

1

Phosphoserine Ref.8 Ref.14

Natural variations

Natural variant

188

1

E → A. Ref.19
Corresponds to variant rs55911801 [ dbSNP | Ensembl ].

VAR_040416

Secondary structure

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350

Helix Strand Turn

Details...

Beta strand

11 – 13

3

Turn

14 – 16

3

Helix

17 – 19

3

Helix

22 – 25

4

Helix

27 – 29

3

Helix

37 – 39

3

Beta strand

40 – 48

9

Beta strand

50 – 59

10

Turn

60 – 63

4

Beta strand

64 – 71

8

Helix

76 – 88

13

Turn

89 – 91

3

Beta strand

98 – 103

6

Turn

105 – 107

3

Beta strand

110 – 115

6

Helix

122 – 125

4

Helix

131 – 150

20

Helix

160 – 162

3

Beta strand

163 – 166

4

Turn

167 – 170

4

Beta strand

171 – 174

4

Helix

196 – 198

3

Helix

201 – 204

4

Helix

213 – 228

16

Beta strand

231 – 234

4

Helix

239 – 250

12

Helix

252 – 261

10

Helix

270 – 273

4

Helix

282 – 285

4

Turn

288 – 290

3

Helix

291 – 293

3

Helix

296 – 305

10

Turn

310 – 312

3

Helix

316 – 320

5

Helix

323 – 325

3

Helix

326 – 331

6

Sequences

	Sequence		Length	Mass (Da)
	P19784 [UniParc]. Last modified February 1, 1991. Version 1. Checksum: 3ECB92F6BD3DD7F1	FASTA	350	41,213
	10 20 30 40 50 60 MPGPAAGSRA RVYAEVNSLR SREYWDYEAH VPSWGNQDDY QLVRKLGRGK YSEVFEAINI 70 80 90 100 110 120 TNNERVVVKI LKPVKKKKIK REVKILENLR GGTNIIKLID TVKDPVSKTP ALVFEYINNT 130 140 150 160 170 180 DFKQLYQILT DFDIRFYMYE LLKALDYCHS KGIMHRDVKP HNVMIDHQQK KLRLIDWGLA 190 200 210 220 230 240 EFYHPAQEYN VRVASRYFKG PELLVDYQMY DYSLDMWSLG CMLASMIFRR EPFFHGQDNY 250 260 270 280 290 300 DQLVRIAKVL GTEELYGYLK KYHIDLDPHF NDILGQHSRK RWENFIHSEN RHLVSPEALD 310 320 330 340 350 LLDKLLRYDH QQRLTAKEAM EHPYFYPVVK EQSQPCADNA VLSSGLTAAR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of human cDNA clones encoding the alpha and the alpha' subunits of casein kinase II." Lozeman F.J., Litchfield D.W., Piening C., Takio K., Walsh K.A., Krebs E.G. Biochemistry 29:8436-8447(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Ovary.
[3]	"A DNA damage-induced p53 serine 392 kinase complex contains CK2, hSpt16, and SSRP1." Keller D.M., Zeng X., Wang Y., Zhang Q.H., Kapoor M., Shu H., Goodman R., Lozano G., Zhao Y., Lu H. Mol. Cell 7:283-292(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH SSRP1 AND SUPT16H.
[4]	"Protein kinase CK2 is involved in G2 arrest and apoptosis following spindle damage in epithelial cells." Sayed M., Pelech S., Wong C., Marotta A., Salh B. Oncogene 20:6994-7005(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CELL CYCLE.
[5]	"p53 serine 392 phosphorylation increases after UV through induction of the assembly of the CK2.hSPT16.SSRP1 complex." Keller D.M., Lu H. J. Biol. Chem. 277:50206-50213(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SSRP1 AND SUPT16H.
[6]	"Caspase-2 primes cancer cells for TRAIL-mediated apoptosis by processing procaspase-8." Shin S., Lee Y., Kim W., Ko H., Choi H., Kim K. EMBO J. 24:3532-3542(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN APOPTOSIS.
[7]	"One-thousand-and-one substrates of protein kinase CK2?" Meggio F., Pinna L.A. FASEB J. 17:349-368(2003) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[8]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18; SER-21 AND SER-288, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"Protein kinase CK2 in health and disease: Protein kinase CK2: from structures to insights." Niefind K., Raaf J., Issinger O.G. Cell. Mol. Life Sci. 66:1800-1816(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON STRUCTURE.
[10]	"Protein kinase CK2 in health and disease: From birth to death: the role of protein kinase CK2 in the regulation of cell proliferation and survival." St-Denis N.A., Litchfield D.W. Cell. Mol. Life Sci. 66:1817-1829(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[11]	"Protein kinase CK2 in health and disease: Cellular functions of protein kinase CK2: a dynamic affair." Filhol O., Cochet C. Cell. Mol. Life Sci. 66:1830-1839(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[12]	"Protein kinase CK2 in health and disease: CK2: the kinase controlling the Hsp90 chaperone machinery." Miyata Y. Cell. Mol. Life Sci. 66:1840-1849(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION IN REGULATION OF HSP90.
[13]	"Protein kinase CK2 in health and disease: CK2 and its role in Wnt and NF-kappaB signaling: linking development and cancer." Dominguez I., Sonenshein G.E., Seldin D.C. Cell. Mol. Life Sci. 66:1850-1857(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION IN WNT SIGNALING.
[14]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-13; SER-18; SER-21 AND SER-288, MASS SPECTROMETRY.
[15]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-97, MASS SPECTROMETRY.
[16]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]	"Structure of human protein kinase CK2 alpha 2 with a potent indazole-derivative inhibitor." Nakaniwa T., Kinoshita T., Sekiguchi Y., Tada T., Nakanishi I., Kitaura K., Suzuki Y., Ohno H., Hirasawa A., Tsujimoto G. Acta Crystallogr. F 65:75-79(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS) OF 1-334 IN COMPLEX WITH INHIBITOR.
[18]	"Structure of the human protein kinase CK2 catalytic subunit CK2alpha' and interaction thermodynamics with the regulatory subunit CK2beta." Bischoff N., Olsen B., Raaf J., Bretner M., Issinger O.G., Niefind K. J. Mol. Biol. 407:1-12(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS).
[19]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ALA-188.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M55268 mRNA. Translation: AAA51548.1.
BC008812 mRNA. Translation: AAH08812.1.

IPI

IPI00020602.

PIR

B35838.

RefSeq

NP_001887.1. NM_001896.2.

UniGene

Hs.82201.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3E3B	X-ray	3.20	X	1-334	[»]
3OFM	X-ray	2.00	A	1-350	[»]
3U87	X-ray	2.90	A/B	331-350	[»]

ProteinModelPortal

P19784.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-318N.

IntAct

P19784. 88 interactions.

MINT

MINT-5004107.

STRING

9606.ENSP00000262506.

PTM databases

PhosphoSite

P19784.

Polymorphism databases

DMDM

125266.

2D gel databases

SWISS-2DPAGE

P19784.

Proteomic databases

PaxDb

P19784.

PeptideAtlas

P19784.

PRIDE

P19784.

Protocols and materials databases

DNASU

1459.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000262506; ENSP00000262506; ENSG00000070770.

GeneID

1459.

KEGG

hsa:1459.

UCSC

uc002enc.3. human.

Organism-specific databases

CTD

1459.

GeneCards

GC16M058191.

HGNC

HGNC:2459. CSNK2A2.

MIM

115442. gene.

neXtProt

NX_P19784.

PharmGKB

PA26959.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000233021.

HOVERGEN

HBG107282.

InParanoid

P19784.

KO

K03097.

OMA

PSWGNQD.

OrthoDB

EOG4J118H.

PhylomeDB

P19784.

Enzyme and pathway databases

BRENDA

2.7.11.1. 2681.

Pathway_Interaction_DB

nfkappabatypicalpathway. Atypical NF-kappaB pathway.
p38alphabetadownstreampathway. Signaling mediated by p38-alpha and p38-beta.

Reactome

REACT_111045. Developmental Biology.
REACT_115566. Cell Cycle.
REACT_21300. Mitotic M-M/G1 phases.

Gene expression databases

ArrayExpress

P19784.

Bgee

P19784.

CleanEx

HS_CSNK2A2.

Genevestigator

P19784.

GermOnline

ENSG00000070770. Homo sapiens.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P19784.

ChEMBL

CHEMBL4070.

ChiTaRS

CSNK2A2. human.

EvolutionaryTrace

P19784.

GenomeRNAi

1459.

NextBio

5997.

SOURCE

Search...

Entry information

Entry name

CSK22_HUMAN

Accession

Primary (citable) accession number: P19784

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	February 1, 1991
Last modified:	May 1, 2013
This is version 139 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.